Published on December 3, 2020
The Meaning of an Enlarged Spleen and Fluctuating Immunoglobulin Levels in CLL Patients
What is the role of the spleen in chronic lymphocytic leukemia (CLL) active observation and treatment? What is the significance of an enlarged spleen? How do you interpret fluctuating immunoglobulin (IG) levels? What is intravenous immunoglobulin (IV)? And finally, can these things cause permanent damage to your immune system?
In this Ask the Expert segment, CLL physician Dr. Nicole Lamanna, MD, Hematologist at Columbia University Herbert Irving Comprehensive Cancer Center, joined by Patient Power co-founder and patient advocate Esther Schorr, will answer these questions and more from our viewers. Keep watching to learn more.
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Transcript | The CLL Spleen and Interpretation of Immunoglobin Levels
Esther Schorr: So, one of the listeners, David Melch, asked a good question. Can you explain the role of the spleen in CLL and issues related to enlarged spleens with patients that are in, you call active observation, as well as in active treatment? And corollary to that question too that came up is, that there are maybe other organs in the body that can get enlarged as a result of CLL and what's the significance of that, if any?
What Does an Enlarged Spleen Mean for CLL Patients?
Dr. Lamanna: When we think about CLL, you think about these lymphocytes and these lymphocytes are in your blood system, right? They are in the bone marrow. But you also have lymph nodes that are part of your hematopoietic blood system and the lymph nodes are also part of that system. Your spleen is like a big lymph node. And so – think of it as, your spleen really helps fight infection, also helps filter your blood from damaged cells, from bacteria and cell waste in your blood.
And for some people, their spleen can be enlarged like a big lymph node because the lymphocytes can actually aggregate in your spleen and so you can have an enlargement that way. There are some people who also have a component of what we call autoimmune thrombocytopenia, where the platelets are very low. And as that happens, as these platelets die in the system and get filtered out from the blood into the spleen, their spleen can become plump that way as well.
And so, your spleen can be enlarged for more than one reason in CLL and similar to lymph nodes, it is not uncommon to have an enlarged spleen with CLL. But if it doesn't bother you or the blood counts are okay, sometimes we do nothing about it. If the spleen becomes so enlarged where it's really occupying a great deal of space and you start losing weight or it's uncomfortable, then the doctor, your physician may say, "I think it's time to treat your disease because your spleen's really large and you're starting to lose weight. You're uncomfortable. You're having difficulty sleeping. It's causing some pain." So those are reasons where we may treat your disease as well, due to a very enlarged spleen – or think of it like in a very large lymph node.
Does Chronic Lymphocytic Leukemia Impact Other Organs?
Since the CLL and the lymphocytes are everywhere, we need you guys all to think of this as, it's in your blood system because people are always asking me, "Where can my CLL go?" Well, it's everywhere. So sometimes if we get biopsies for other indications, let's say you have a random biopsy of something else in your body and there are lymphocytes, then they see CLL cells, of course it's going to be there. So, not to panic. So similarly, the liver can also have your lymphocytes in the liver and the liver can be enlarged for that reason too. So similarly, those are the most common organs that CLL cells can be.
Think of the spleen as it really helps fight infection and when the spleen gets enlarged, it could cause some issues with the person that might need treatment because of an occupying space issue, and it can have a role in the autoimmune issues as well.
Esther Schorr: But having an enlarged spleen doesn't necessarily trigger treatment for everybody.
Dr. Lamanna: No.
Esther Schorr: It's an indication that, that needs to be watched.
Dr. Lamanna: Yes. Absolutely. Just similar to your white count, which the doctor watches, right? Or the lymph nodes, if the lymph nodes, you have some enlarged lymph nodes but they're not bothering you. By having the presence of an enlarged spleen doesn't mean you need treatment right away. It's going to be taken into context with the rest of your disease as well.
What is the Significance of Fluctuating Immunoglobulin (IG) Levels?
So it is common in CLL patients that their immunoglobulin levels are low. And in fact, at diagnosis probably a good 25% are low and then the longer that somebody has CLL, the majority of patients, their immunoglobulin levels can become low over time. Now, interestingly enough, there's a lot we don't know about this. In other words that these are... So, think of your immunoglobulin levels again – are one aspect of your immune system to help fight infections. However, they are not the end all, the be all. This just happens to be one test that we can actually draw of your blood that we can actually look at.
Many patients have low levels but that doesn't mean all our CLL patients with low levels get infections. Think of it like it's a cheap surrogate marker to look at your immune system but by no means is it totally inclusive because we don't understand well, so how come this person has low levels and never gets a cold and this person always gets sick? So, it's one measurement of your immune status but by no means is it all encompassing. And so, we're actually trying to learn about this.
What is Intravenous Immunoglobulin (IVIG)?
So oftentimes, we'll give gamma globulin replacement therapy to our CLL folks who are constantly running into issues with infection all the time, whether they get hospitalizations for pneumonia or sinusitis, constantly needing oral antibiotics. Those are prime candidates that will think about gamma globulin replacement therapy because otherwise, we'd be giving practically many of our CLL patients, probably most of our CLL patients IVIG. It's extremely expensive and it commits them to – it's an infusion or subcutaneous injection once a month.
There'll be some future clinical trials actually looking at trying to give IVIG to patients versus not and seeing whether or not we really impact the decrease of infectious outcomes and how long do we use it for. These are all unanswered questions. So many of us do this sort of intuitively. So, what we've been doing for years, who we think needs it.
But there's not a lot of good data about how long should we administer IVIG, who are the right candidates? Does it really decrease infections? Bacterial versus fungal versus viral. So, this is all stuff we need to learn. So yes, it is true. Many patients with CLL have low levels, usually IgG and IgA and then some can even have all of them low, and the indications to replete it usually is if their IgG is less than 500. But usually going along with infectious issues, not just repleting it to replete low levels.
Now when you talked about therapies, I'll just touch upon that briefly. That traditional therapies for CLL, so more chemoimmunotherapy based fludarabine (Fludara), those types of treatments, typically when somebody would get those treatments, their immunoglobulin levels would also stay low due to the treatment itself. Now in the era of some of these novel more targeted therapies, like the BTK inhibitors and venetoclax (Venclexta), there's some suggestion that the immunoglobulin levels may not decrease as much, some of them may improve. I think we need more data on that following, do levels change on long-term use of some of the oral therapies?
But I think more importantly, regardless of chemoimmunotherapy versus novel agents, I think what's important is often times when patients start getting into trouble from their CLL and their infections increase, that A: having a trial of IVIG I think is appropriate. But B is, even in the short run if you get chemotherapy and your immunoglobulin levels decrease let's say, if somebody got fludarabine. If you treat the CLL, oftentimes your immune system does improve.
So again, the immunoglobulin levels aren't just one thing that should be measured. But the point is, is that the levels are only one sort of cheap surrogate marker to look at infections. There's a lot of other cells that support you and your body with dealing with infections. And we just don't have a very good way or measuring all this.
Can Low Immunoglobulin Levels from CLL Permanently Damage Your Immune System?
No. Your system can rebound. The question is, I guess, one of the things that we don't know is, how much improvement do we see in patient’s immunoglobulin levels over time depending upon the different treatment options. And that's what I was saying, that with some of the more novel agents, there's been some data suggesting that their immunoglobulin levels may improve but I don't think we have any definitive publication from any of us that has looked at levels specifically and said, "Oh look. This definitely improves,” or not. I think we all talk about the infections, which is really what… is a correlate to those levels.
So, I guess what I would say to those folks is, I don't want you to think that your immune system is permanently damaged, but particularly if your CLL is being treated and you’re doing well, it's probably improving but the levels may not always justify or levels may not always correlate with your improvement to the other parts of your immune system that I was talking about, that we can't test for. And so, I think, the most important take away at home is that not everybody needs IVIG. Hopefully, we'll learn how to better use it, but some people could benefit from it.
And if you have infections that are ongoing, absolutely that's what's important, right? So if you're really having infectious complications, those are the issues that you need to talk to your doctor about, right? Because that's what I'm going to want to know is how often you're getting sick, how often do I need to give you medicine or not medicine because is that correlating with disease progression because your immune system is really not handling things well and maybe your numbers may not be that bad. But do I need to think about treatment for you because your immune system is really not letting you overcome infections and things like that. So, infections are important to report to your doctor.
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